As insulin resistance and NIDDM may both have a genetic basis, we are searching systematically for the involved gene(s) using sib-pair linkage analyses of evenly spaced microsatellite markers in the Pima Indians of the Gila River Indian Community, a population with the highest known prevalence of this disease. We found evidence for linkage and association of insulin resistance and NIDDM with a cluster of microsatellite markers within a 2-3 cM genomic segment at the 7q21.3- q22.1 chromosomal band. In addition, marker D7S479, linked with NIDDM in the Pimas, is also linked with NIDDM in families of Northern European descent living in Utah. Based on these findings we conclude that there is a genetic element in the region 7q21.3-q22.1 contributing to diabetes susceptibility. Studies are in progress to identify this gene.